A Situational Analysis of Competences of Research Ethics Committee Members in Review of Research Protocols with Complex and New Study Designs in Uganda

BACKGROUND Over the past two decades, Uganda has experienced a signicant increase in clinical research driven by both industry and the need to combat the emergence and re-emergence of infectious disease epidemics. This has broadened the spectrum of research proposals that need evaluation by Research Ethics Committees (RECs) with associated requirement for new expertise. We assessed the competencies of REC members in review of research protocols with complex and new research study designs to guide development of a training curriculum to improve the quality of review. METHODS This was a cross-sectional study design, with quantitative and qualitative data collection methods. We used a structured pre-coded questionnaire to collect data on competencies of REC members in review of research protocols with complex and new research study designs. Research Ethics Committee members were also asked to outline a list of additional topics for which they needed training. Data from coded questions was entered into Epidata Version 3.1 and then exported to STATA Version14.1 for analysis. Descriptive analysis was performed for quantitative data and ndings were presented using percentages and frequencies. RESULTS We enrolled 55/97 REC members from 6 RECs, majority of whom were males (56.4%, n= 31/55). The level of competence for review of selected study design was lowest for Controlled Human Infection Model (6, 10.9%) and reverse pharmacology design (6, 10.9%,), and highest for cluster randomized study design (29, 52.7%) and implementation science research (29, 52.7%). CONCLUSION There is lack of competence in review of research protocols with complex and new study design and our analysis suggests that additional training in this area is an urgent priority.


Background
Clinical research remains cardinal in advancing our knowledge of disease, human biology and behavior and informing our health care practice (1). There has been a surge in clinical research driven by both industry and the need to combat the emergence and re-emergence of infectious disease epidemics in Uganda, including HIV, hemorrhagic fevers, tuberculosis, malaria, neglected tropical diseases, noncommunicable diseases and the recent Severe Acute Respiratory Syndrome Corona Virus-2 that causes Corona virus disease-19 (COVID-19) (2)(3)(4)(5). This has broadened the spectrum of research activities in the quest for solutions to improve health and wellbeing. Clinical research, especially that involve invasive procedures and interventions, may carry risks to human health and safety or may compromise the rights, values and interests of research participants or volunteers (6). Nonetheless, human participation in clinical research is important, and every effort should be made to minimize harm to research participants (6).
With the introduction of antiretroviral therapy, scientists in Uganda embarked on clinical trials with adherence and long-term e cacy monitoring (7,8). In the recent past; there has been increasing interest in HIV vaccines research and investigations into a cure for HIV (9). These research interests to develop novel preventive, investigational and treatment strategies need to be supported by e cient RECs to review the science and ethics, approve and monitor research regulatory compliance with assurance for safety and wellbeing of humans as research participants.
Members of RECs review the science and ethics of research proposals, approve research protocols and oversee the conduct of clinical research with the aim of minimizing risk to humans and ensuring respect for the research participant's rights, values and interests (10).
It is therefore important, to ensure that members of RECs have the competence to review research protocols to protect the safety, rights and welfare of research participants while advancing knowledge through high quality research. Therefore, this study aimed to assess the competencies of REC members in review of research protocols with complex and new research study designs, in order to guide

Study procedure
The REC Chairs were contacted and informed about the study. The list of REC members was obtained from the REC administrators with contact details: email and phone number. Convenience sampling was used to enrol participants. Participants were selected based on availability and willingness to take part in the assessment. A notice was sent to each participating REC member and an appointment for the study interview made. Written informed consent form was obtained from the participants before the conduct of the face-to-face interview. However, due to the COVID-19 lock-down restriction measures enforced by the Uganda Ministry of Health, the data collection method was changed from face-face paper basedquestionnaire to an online survey using KoBoToolbox. An email with a link to the online Informed Consent Form and the survey were sent to REC members inviting them to participate in the survey. In order to increase on the response rate, email and telephonic reminders were sent for participants who had not lled the survey after 7 and at 14 days of sending the survey.

Data collection
Data were collected using a pre-coded questionnaire developed for this study in English language.

Discussion
We assessed the competencies of REC members in review of research protocols with complex and new research study designs to guide development of a training curriculum to improve the quality of review.
The response rate amongst REC members in this study was slightly higher compared to 52% in a similar study in a similar setting (11). The ratio of male to female participants was almost equal, which could be attributed to the guidelines by the Uganda National council for Science and Technology which encourage RECs to have diverse membership, including consideration of gender (10). Majority of the participants had a master's degree or higher quali cation. This is attributed to the national guidelines requirement that the REC to be su ciently quali ed through the experience and expertise in different specialty areas (10).
Most participants reported that they were not competent to review research protocols with complex and new study designs. Our ndings are in agreement with the discussion highlighted during the 10th Annual National Research Ethics Conference, that emergence of new study designs like Controlled Human Infection Model, studies with digital intervention and genetic studies present enormous scienti c and ethical challenges for review by REC members (12)(13)(14)(15). The lack of competence in review of research protocols with complex and new study design could lead to a longer or delayed research review process, poor quality review and rejection of important studies. The lack of competence reported could be due to broadened spectrum of research emanating from signi cant increase in clinical research that is driven by the changing disease patterns.

Limitations Of The Study
There may be some possible limitations of this study. The small sample size which we attribute to the impact of COVID-19 restrictive measures affected our analysis and conclusions. In addition, the RECs involved are situated in the capital city of Uganda, Kampala, where most research institutions are located thus the results may not be generalisable to all RECs in the country due to differences in the volumes and scope of the research received by these RECs and the academic environment.

Conclusion And Recommendation
There is lack of competence in review of complex and new study design among the REC members studied and additional training in this area is an urgent priority. Results of this study will inform development of a training curriculum for REC members in Uganda. Written consent was obtained before the survey was undertaken for the surveys that were collected using a paper-based form of data collection. For the online survey, the e-consent form provided detailed information about the survey. Individuals who voluntarily choose to participate clicked on a box "I agree to participate" and those not willing will click on "I do not agree to participate". E-consent was not taken as a "full signature" but rather an indication of accepting to participate in the survey.

List Of Abbreviations
Consent for publication: Not applicable. The manuscript does not contain data from any individual person's data.
Availability of data and materials: The datasets used and/or analyzed during the current study are available from the corresponding author on a reasonable request. All data generated or analyzed during this study are included in this published article.
Competing interests: Authors declare that there are no competing interests Funding: The study is supported by the Ethics project entitled "Towards eliminating HIV in Uganda by 2030; Preparing Ethical Review Committees to support this agenda" at the Infectious Diseases Institute, which is, funded the National Institutes of Health (1 G11 TW011309-01). The funding bodies did not have a role in the design of the study and collection, analysis, and interpretation of data and in writing the manuscript.